This grant represents a multidisciplinary effort of a microbiologist, a behavioral biologist, an organic chemist, a histofluorescent microscopist, a biochemical psychiatrist, and a biophysical-biochemical kineticist (and staff), working in concert to develop new concepts in neurobiological regulation in relationship to the actions of drugs of abuse. Findings thus far emerging from the center include: (1) endogenous brain detoxification mechanisms for drugs of abuse; (2) Neurometabolic adaptive mechanisms in the serotonergic, dopaminergic, noradrenergic, and cholinergic systems in the brain to drugs of abuse; (3) behavioral correlates of the above adaptive mechanisms; (4) new and specific anatomical correlates of the above adaptive mechanisms; (5) new and specific anatomical representations of the location and relationship between locations of these adaptive mechanisms; and (6) a new kind of CNS neurotransmitter biosynthetic enzyme kinetics, involved with adaptive mechanisms (which have heretofore been unreported in brain). Each separate section represents basic and sequential research in its own area, and the center as a whole represents an interdisciplinary research effort on many fronts to more carefully characterize the basic mechanisms involved with drugs of abuse. The combination of single and sequential research themes, as well as cross-sectional interactional research themes, represent we think one of the unique aspects of our center to which we invite the attention of the grant reviewers.